High sensitivity and amenability to miniaturization for field-portable applications have helped to make ion mobility spectrometry (IMS) an important technique for the detection of many compounds, including narcotics, explosives, and chemical warfare agents as described, for example, by G. Eiceman and Z. Karpas in their book entitled “Ion Mobility Spectrometry” (CRC, Boca Raton, 1994), which is incorporated by reference herein. In IMS, gas-phase ion mobilities are determined using a drift tube with a constant electric field. Ions are separated in the drift tube on the basis of differences in their drift velocities. At low electric field strength, for example 200 V/cm, the drift velocity of an ion is proportional to the applied electric field strength, and the mobility, K, which is determined from experimentation, is independent of the applied electric field. Additionally, in IMS the ions travel through a bath gas that is at sufficiently high pressure that the ions rapidly reach constant velocity when driven by the force of an electric field that is constant both in time and location. This is to be clearly distinguished from those techniques, most of which are related to mass spectrometry, in which the gas pressure is sufficiently low that, if under the influence of a constant electric field, the ions continue to accelerate.
E. A. Mason and E. W. McDaniel in their book entitled “Transport Properties of Ions in Gases” (Wiley, N.Y., 1988), which is incorporated by reference herein, teach that at high electric field strength, for instance fields stronger than approximately 5,000 V/cm, the ion drift velocity is no longer directly proportional to the applied electric field, and K is better represented by KH, a non-constant high field mobility term. The dependence of KH on the applied electric field has been the basis for the development of high field asymmetric waveform ion mobility spectrometry (FAIMS). Ions are separated in FAIMS on the basis of a difference in the mobility of an ion at high field strength, KH, relative to the mobility of the ion at low field strength, K. In other words, the ions are separated due to the compound dependent behavior of KH as a function of the applied electric field strength.
In general, a device for separating ions according to the FAIMS principle has an analyzer region that is defined by a space between first and second spaced-apart electrodes. The first electrode is maintained at a selected dc voltage, often at ground potential, while the second electrode has an asymmetric waveform V(t) applied to it. The asymmetric waveform V(t) is composed of a repeating pattern including a high voltage component, VH, lasting for a short period of time tH and a lower voltage component, VL, of opposite polarity, lasting a longer period of time tL. The waveform is synthesized such that the integrated voltage-time product, and thus the field-time product, applied to the second electrode during each complete cycle of the waveform is zero, for instance VHtH+VLtL=0; for example +2000 V for 10 μs followed by −1000 V for 20 μs. The peak voltage during the shorter, high voltage portion of the waveform is called the “dispersion voltage” or DV, which is identically referred to as the applied asymmetric waveform voltage.
Generally, the ions that are to be separated are entrained in a stream of gas flowing through the FAIMS analyzer region, for example between a pair of horizontally oriented, spaced-apart electrodes. Accordingly, the net motion of an ion within the analyzer region is the sum of a horizontal x-axis component due to the stream of gas and a transverse y-axis component due to the applied electric field. During the high voltage portion of the waveform, an ion moves with a y-axis velocity component given by vH=KHEH, where EH is the applied field, and KH is the high field ion mobility under operating electric field, pressure and temperature conditions. The distance traveled by the ion during the high voltage portion of the waveform is given by dH=vHtH=KHEHtH, where tH is the time period of the applied high voltage. During the longer duration, opposite polarity, low voltage portion of the asymmetric waveform, the y-axis velocity component of the ion is vL=KEL, where K is the low field ion mobility under operating pressure and temperature conditions. The distance traveled is dL=vLtL=KELtL. Since the asymmetric waveform ensures that (VHtH)+(VLtL)=0, the field-time products EHtH and ELtL are equal in magnitude. Thus, if KH and K are identical, dH and dL are equal, and the ion is returned to its original position along the y-axis during the negative cycle of the waveform. If at EH the mobility KH>K, the ion experiences a net displacement from its original position relative to the y-axis. For example, if a positive ion travels farther during the positive portion of the waveform, for instance dH>dL, then the ion migrates away from the second electrode and eventually will be neutralized at the first electrode.
In order to reverse the transverse drift of the positive ion in the above example, a constant negative dc voltage is applied to the second electrode (superimposed upon the asymmetric waveform). The difference between the dc voltage that is applied to the first electrode and the dc voltage that is applied to the second electrode is called the “compensation voltage” (CV). The CV prevents the ion from migrating toward either the second or the first electrode. If ions derived from two compounds respond differently to the applied high strength electric fields, the ratio of KH to K may be different for each compound. Consequently, the magnitude of the CV that is necessary to prevent the drift of the ion toward either electrode is also different for each compound. Ideally, when a mixture including several species of ions, each with a unique KH/K ratio, is being analyzed by FAIMS, only one species of ion is selectively transmitted to a detector for a given combination of CV and DV. In one type of FAIMS experiment, the applied CV is scanned with time, for instance the CV is slowly ramped or optionally the CV is stepped from one voltage to a next voltage, and a resulting intensity of transmitted ions is measured. In this way a CV spectrum showing the total ion current as a function of CV, is obtained.
In practice, a mixture of ions may include two different species of ions that cannot be separated according to the FAIMS principle alone. For instance, the two different species of ions may have coincidentally substantially an identical ratio of high field mobility to low field mobility (same KH/K ratio), and thus each species of ion is “selectively” transmitted at a same given combination of CV and DV. For example, a first type of ion has a low field mobility of 2.0 but at high value of E/N this mobility is increased by 5% so that the high field mobility is 2.1 cm2/Vs. A second type of ion in this example has a low field mobility of 2.2 but at high E/N the mobility also increases by 5% so that the high field mobility is 2.31 cm2/Vs. The two ions have different mobility at low field and also have different mobility at high field, but coincidentally the ratio of high field mobility to low field mobility is identical. In this example KH/K for both ions is 1.05. In such a case, the CV spectrum peak corresponding to one of the two different species of ions overlaps completely or partially with the CV spectrum peak corresponding to the other of the two different species of ions.
Problems may also be encountered when the two different species of ions have similar but non-identical ratio of high field mobility to low field mobility (similar KH/K ratio). In this case, FAIMS may be unable to resolve the two different species of ions. The resolution of a FAIMS device is defined in terms of the extent to which ions having similar mobility properties as a function of electric field strength are separated under a set of predetermined operating conditions. In the example above, the two types of ions both had KH/K ratios of 1.05 and could not be separated by FAIMS. In another case however, two other types of ions, which are less than identical, may have KH/K ratios of 1.05 and 1.055. Yet another pair may have ratios that differ even more widely, for example 1.02 and 1.09. Thus, a high-resolution FAIMS device transmits selectively a relatively small range of different ion species having similar mobility properties (KH/K ratios of these ions are very similar to each other), whereas a low-resolution FAIMS device transmits selectively a relatively large range of different ion species having less-similar mobility properties (KH/K ratios of these ions may differ from each other by a wider margin). For instance, the resolution of FAIMS in a cylindrical geometry FAIMS is compromised relative to the resolution in a parallel plate geometry FAIMS, because the cylindrical geometry FAIMS has the capability of focusing ions. This focusing action means that ions of a wider range of mobility characteristics are simultaneously transmitted within the analyzer region of the cylindrical geometry FAIMS. A cylindrical geometry FAIMS with narrow electrodes has the strongest focusing action, but the lowest resolution for separating ions. As the radii of curvature are increased, the focusing action becomes weaker, and the ability of FAIMS to simultaneously focus ions of similar high-field mobility characteristics is similarly decreased. This means that the resolution of FAIMS increases as the radii of the electrodes are increased, with parallel plate geometry FAIMS expected to have the maximum attainable resolution.
It is known to provide a second analyzer in tandem with FAIMS. For instance, in co-pending U.S. patent application Ser. No. 10/220,603, which was filed on Sep. 3, 2002 and is incorporated by reference herein, a tandem FAIMS/ion mobility spectrometer is described. Ions are provided via an outlet from a FAIMS analyzer into a separate ion mobility analyzer, such as for instance a drift tube ion mobility spectrometer (DTIMS). Accordingly, ions that may not be separated on the basis of differences in high field ion mobility behavior using FAIMS may never the less be separated on the basis of their absolute low-field ion mobility properties using DTIMS. Unfortunately, each analyzer has finite transmission efficiency, such that some of the ions of interest are lost during analysis within each of the two separate analyzers. Furthermore, transmission of ions from one analyzer to another analyzer also results in loss of some of the ions of interest due to collisions with electrode surfaces near the analyzer outlet or inlet. The overall result is low effective ion transmission efficiency and correspondingly low sensitivity. It is a further disadvantage of the above-mentioned system that additional time is required to separate ions using separate FAIMS and DTIMS analyzers. It is also a disadvantage of the above-mentioned system that the ions pass through DTIMS in packets which arrive at the end of the drift tube as a function of time, and therefore add a requirement of specialized detection and analysis systems to interpret this signal. In this last example an expensive TOF mass spectrometer is typically employed to detect ions from a DTIMS, rather than a less-expensive quadrupole mass spectrometer.
Although a separation of ions using the FAIMS approach has significant value for simplification of complex mixtures, in some instances further separation capability is desirable. As discussed supra ions are separated in FAIMS on the basis of a field dependent change of the mobility properties of the ions. Accordingly, it may sometimes occur that a first species of ion and a second species of ion will have substantially identical field dependent changes of the mobility properties. In such a case, the first species of ion and the second species of ion cannot be separated using the FAIMS approach alone. Furthermore, small cylindrical FAIMS electrodes are known to achieve improved ion focusing capability at the expense of resolution. Accordingly, there is an ongoing need for a method of separating ions that overcomes some of the limitations of the prior art.